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Absorption
After you inject insulin, it goes into the bloodstream to work. If the insulin is R/neutral or one of the non-mixed analogs, it will be absorbed quickly. Fast-acting insulins are designed to be absorbed even faster, while insulin suspensions are made to "hinder" the rapid absorption of the insulin, to make them work for a longer time period. Neutral Neutral or R insulin is close to the natural form of insulin and has a normal absorption profile. Insulin molecules clump together naturally into "hexamers" (groups of six), which then drift apart when sufficiently diluted. The clumped form cannot be used directly, so there's a bit of time delay using R insulin. Faster-acting It is possible to "speed" the absorption of insulin; one way is to alter the amino acid sequence(s) of them, producing analog insulins like Humalog, Novolog, NovoRapid and Apidra. Some of these (Humalog, Novolog) work by substituting or exchanging one or two amino acids near position B28 so that insulin molecules will tend to remain separate instead of allowing them to clump together naturally into hexamers. Using these types of alterations to force the insulin molecules to dissociate (remain apart, in the form of dimers and monomers, rather than their natural tendency to stay together), means they will be absorbed by the body faster. It might be easier to visualize this by thinking of a whole pie, slicing it into 6 pieces and putting one slice each on separate plates. The pie can't be eaten until it has been cut and served on plates. Another way of forcing the insulin hexamers to stay apart is with a less then U100 strength of insulin. The "Strength" section of the insulin page deals in depth with this concept. Slower-acting Other insulins, whether suspended or not, contain minute crystals of varying sizes which are deposited under the skin with the injection. Those with larger crystals, such as Ultralente, are absorbed slower than those with microfine ones, such as Semilente. Lente-type insulins are a "blend" of 30% faster-acting semilente crystals and 70% slower-acting Ultralente ones; this produces an intermediate-acting insulin. Mixed insulins are combined with a protamine suspension to keep them from being absorbed rapidly. Though it is not a suspended insulin, Lantus delays its absorption by not forming crystals until AFTER it has been injected. Lantus's suspension is a special acidic preparation (pH 4.0) that reacts with the injection site forming micro-precipitates around the insulin crystals, which keeps them trapped for a while. Once the crystals make it to the bloodstream, they're absorbed as fast as any other insulin. Don't rub the injection site after injection or you can speed up absorption of Lantus and all other insulinsInsulin-Dependent Diabetes-Dr. Ragnar Hanas (Pages 12 & 13). Of course it's usually not recommended to rub the injection site in any case. Levemir uses an ordinary protamine suspension but has a genetically-engineered sticky "acyl side chain" that clings for a while to albumin (protein) molecules found in the bloodstream (and under the skin) that makes the Levemir molecule too big to enter/exit the bloodstream and therefore slows down its absorption, not only at the site but also in the bloodstream and at the target tissues. It is also possible to delay the absorption of an insulin by increasing its strength. U500 insulin, which is five times more concentrated than U100, has been available through both Lilly and Novo Nordisk(Note: Their similar product is U400 strength insulinUse of U500 Insulin in Patients With Extreme Insulin Resistance-Diabetes Care-ADA-2005) by special order for many years. The insulin's main use is for people with extreme Insulin resistance, and is commercially available only in R/Neutral type. Though it is R/Neutral-type insulin, U400 & U500 insulins have a pharmacokinetic more like NPH insulin than U100 R/Neutral. Since there are no additives such as suspensions to alter R/Neutral insulin's action, the strength of the insulin formula hinders its breakdown into dimers and monomers, thus making it much slower-absorbed than U100 and lesser strength insulinsFive Fold Increase of Insulin Concentration Delays the Absorption of Human Insulin Injections in Pigs-Diabetes Research & Clinical Practice-2000Use of U500 R Insulin by Continuous Insulin Infusion (Insulin Pump)in Patients With Type 2 Diabetes & Severe Insulin Resistance Endocrine Practice-2006. Effect of origin People absorb r-DNA/GE/GM insulin at a faster rate than either pork or beef insulin, because it is an exact amino acid match to their own. They absorb pork insulin a bit slower, because it is one amino acid away from theirs. Slowest of all is beef insulin, as it is three amino acids away from a person's natural insulin. It would be exactly opposite for dogs because their natural insulin is a perfect match to pork insulin, and one amino acid away from r-DNA/GE/GM insulin. Dogs would absorb pork insulin faster than r-DNA/GE/GM human insulin. They would absorb beef insulin slower than either pork or r-DNA/GE/GM human insulin, as it is two amino acids away from a perfect match to their own. Beef insulin, which is quite slow for human beings, owing to the three amino acid difference between beef insulin and a human's own, would act more rapidly in cats, since it is the closest match we have to native feline insulin until r-DNA/GE/GM feline insulin comes along. Cats would absorb pork insulin slower than beef because of the 3 amino acid differences between them; they would absorb r-DNA/GE/GM human insulin slowest of all, because there are 4 amino acid differences in feline and human insulin. Insulin Amino Acid Differences Effect of injection site Taking absorption outside the lab, many other factors come into play. A study done at the University of Minnesota showed that there is an 29-39% variation on the amount of insulin going into the bloodstream from one day to another Day To Day Variability Of Insulin. Some diabetic cat caregivers report differing absorption rates with the same insulin depending on the injection site, the shot technique, and the needle length on the syringe. Levemir is too new to show any feline or canine data, but the manufacturer claimsNovo Nordisk Presentation--Less Variability that in their testing on humans they found much lower day-to-day variability Lower Day-to-Day Variability, even when shooting at different sites. They claim that this is because the Levemir "clinging" actionLevemir "Clinging" Action Movie takes place throughout the body and in the blood, and so is not dependent on injection site conditions. Effect of body condition Cats and dogs who are dehydrated may have reduced insulin absorption rates (need source). Other factors modulating insulin absorptionInsulin in the Hospital Setting, Ira B. Hirsch, U of Washington Medical Center include regional blood flow which is affected by exercise, rubbing or massage, and temperature. Further Reading *Mechanism for Novolog (pdf) *Mechanism for Humalog (pdf) *A chart of the variations in amino acid sequence on the A and B chains of different species *Absorption Kinetics of Regular, Isophane & Protamine Zinc Insulin in Normal Cats-Domestic Animal Endocrinology-1990 *Comparison of 2 Ultralente Insulin Preparations (Human & Beef/Pork)With Protamine Zinc (Beef/Pork) Insulin in Clinically Normal Cats-American Journal of Veterinary Research-1994 References Category:InsulinsCategory:Terms